Salivary Gland (SG) Cancers are a rare and heterogeneous group of tumors, usually approached by multidisciplinary teams in high specialized centers. Until today no standard of care exists to treat these cancers. The identification of a target, the androgen receptor, in SG tumors has allowed for new treatment strategies options for this rare group of diseases. As a matter of fact, strong positivity for androgen expression has been found in salivary duct carcinoma and adenocarcinomas. The purpose of this study is therefore to evaluate the efficacy and safety of chemotherapy versus androgen deprivation therapy (ADT) in patients with recurrent and/or metastatic AR expressing SGCs.

The study will include two cohorts of patients: Cohort A, which comprises chemo-naïve patients, and Cohort B, which comprises pretreated patients.

Overall Survival (OS) [ Time Frame: 37 months after First Patient In ]

Adverse Events according to CTCAE v4.0 [ Time Frame: 37 months after First Patient In ]

adverse events will be recorded using International Common Terminology Criteria for Adverse Events (CTCAE), version 4.0, the investigator will assess whether those events are drug related (reasonable possibility, no reasonable possibility) and this assessment will be recorded in the database for all adverse events

Patients from cohort A (chemonaïve) may be randomized in this arm to receive chemotherapy

Drug: Cisplatin + Doxorubicin
Drug: Carboplatin + Paclitaxel

Experimental: Androgen Deprivation Therapy (ADT)

ADT = bicalutamide + triptorelin

Patients from cohort A (chemonaive) may be randomized to receive ADT, and patients from cohort B (pre-treated) will receive ADT without having been randomized.

Drug: bicalutamide + triptorelin

Detailed Description:

Patients in Cohort A will be randomized 1:1 at the study entry to receive ADT (triptorelin + bicalutamide 50 mg) or standard chemotherapy. Patients of Cohort A randomized to the control arm (chemotherapy arm) will be given the option to enter Cohort B at the time of disease progression. As long as Cohort A is open to recruitment, patients who will be treated by chemotherapy will be simultaneously enrolled in Cohort B. Accrual in Cohort B will be stopped when recruitment of 76 eligible patients in Cohort A is reached.

Adequate cardiac function as demonstrated by a clinically normal 12 lead ECG; additionally for patients who will receive Cisplatin and Doxorubicin adequate cardiac function should be demonstrated by a left ventricular ejection fraction (LVEF) ≥ 50% (within 2 weeks prior to treatment start)

Exclusion Criteria:

Actively bleeding tumor if the patient is intended to be treated with carboplatin

Patients with bone disease or brain disease as the sole disease site; brain metastases are allowed in case of systemic disease, but must have been treated at least 4 weeks before enrollment and must be stable after that;

previous cardiac toxicity induced by another anthracycline or previous exposure to maximum cumulative dose of another anthracycline if the patient is intended to be treated with doxorubicin

history of allergic reactions attributed to compounds of similar chemical or biological composition to cis/carboplatin, paclitaxel, doxorubicin, bicalutamide or triptorelin;

concomitant medications with terfenadine, astemizole, cisaprid

use of phenytoin

Patients who received vaccine for yellow fever

active second malignancy during the last five years except non melanomatous skin cancer or carcinoma in situ of the cervix;

positive serum pregnancy test within 1 week prior to the first dose of study treatment for Women of child bearing potential (WOCBP);

no adequate birth control measures, as defined by the investigator, during the study treatment period and for at least 6 months after the last study treatment for patients of childbearing / reproductive potential.

psychological, familiar, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule; those conditions should be discussed with the patient before registration in the trial;

written informed consent not given according to ICH/GCP, and national/local regulations, before patient registration

participation in another interventional clinical trial in the preceding 4 weeks prior to randomization

for cohort A patients: previous chemotherapy for recurrent/metastatic disease (previous chemotherapy given concomitantly with RT in the past is allowed, including cisplatin but it should be completed at least 6 months before enrollment).

Contacts and Locations

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Please refer to this study by its ClinicalTrials.gov identifier: NCT01969578